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Masakazu Takayasu and Ralph G. Dacey Jr.

✓ An isolated cerebral arteriole preparation was used to test the hypothesis that a temporary reduction in transmural pressure causes a subsequent vasodilation mediated by mechanisms intrinsic to the vessel wall. Thirty-five cerebral vessels of 44.7 ± 1.4 µm (± standard error of the mean) mean diameter were cannulated in vitro and pressurized at a transmural pressure of 60 mm Hg; after an equilibration period the vessels developed spontaneous tone. When transmural pressure was decreased to 0 mm Hg for a period of 4 minutes then returned to 60 mm Hg, vessels dilated to 155.1% ± 6.8% of control diameter before gradually redeveloping spontaneous tone in 5.5 ± 0.7 minutes. Varying the duration of the period during which transmural pressure was at 0 mm Hg had no significant effect on the degree of vasodilation. Conversely, varying the level of decreased transmural pressure between 0 and 20 mm Hg significantly affected both the magnitude of vasodilation and the time course of spontaneous tone recovery. These findings indicate that a temporary period of decreased transmural pressure may result in a loss of spontaneous tone in the resistance vessels of the cerebral microcirculation. Mechanisms intrinsic to the vessel wall may play a significant role in the early stage of post-reperfusion hyperemia. Such mechanisms could also be implicated in other hyperemic phenomena affecting the cerebral circulation, such as the rapid increase in intracranial pressure after subarachnoid hemorrhage, the development of the normal perfusion pressure breakthrough phenomenon, and the initiation of intracranial pressure plateau waves.

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Dennis G. Vollmer, Masakazu Takayasu, and Ralph G. Dacey Jr.

✓ The reactivity of rabbit basilar artery and penetrating arteriolar microvessels was studied in vitro using an isometric-tension measurement technique and an isolated perfused arteriole preparation, respectively. Comparisons were made between reactivities of normal vessels and those obtained from animals subjected to experimental subarachnoid hemorrhage (SAH) 3 days prior to examination. Subarachnoid hemorrhage produced significant increases in basilar artery contraction in response to increasing concentrations of serotonin (5-hydroxytryptamine) (10−9 to 10−5 M) and prostaglandin F (10−9 to 10−5 M) when compared to normal arteries. In addition, SAH attenuated the relaxing effect of acetylcholine following serotonin-induced contraction and of adenosine triphosphate after KCl-induced basilar artery contractions. In contrast to the changes observed in large arteries, cerebral microvessels did not demonstrate significant differences in spontaneous tone or in reactivity to a number of vasoactive stimuli including application of calcium, serotonin, and acetylcholine. On the other hand, small but significant changes in arteriolar responsiveness to changes in extraluminal pH and to application of KCl were noted.

Findings from this study suggest that intracerebral resistance vessels of the cerebral microcirculation are not greatly affected by the presence of subarachnoid clot, in contrast to the large arteries in the basal subarachnoid space. The small changes that do occur are qualitatively different from those observed for large arteries. These findings are consistent with the observation of significant therapeutic benefit with the use of calcium channel blockers without changes in angiographically visible vasospasm in large vessels. It is likely, therefore, that calcium antagonists may act to decrease total cerebrovascular resistance at the level of the relatively unaffected microcirculation after SAH without changing large vessel diameter.

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Michael R. Chicoine, Alexander T. Yahanda, and Ralph G. Dacey Jr.

Donald Simpson (1927–2018) was a neurosurgeon from Adelaide, Australia, who is often cited for the 1957 publication he wrote as a trainee on the relationship between extent of resection and outcomes for meningiomas. That paper summarized a series of over 300 patients operated on in England by well-known neurosurgeons Sir Hugh Cairns and Joseph Buford Pennybacker. Simpson was also known later in his career, when he was at the University of Adelaide in South Australia, for his contributions to the areas of hydrocephalus, spina bifida, craniofacial anomalies, head injury, brain abscesses, and neurosurgical history, and he published extensively on these topics. In addition to his work in clinical neurosurgery, Simpson made humanitarian contributions studying kuru in New Guinea and aiding refugees during the Vietnam War. Simpson was an active member and leader of many Australian surgical organizations and was an officer of the Order of Australia. Donald Simpson’s legacy as an adult and pediatric neurosurgeon, an academician, a leader, and a humanitarian is extensive and will prove long lasting. Professor Simpson’s life serves as an example from which all neurosurgeons may learn.

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S. Kathleen Bandt and Ralph G. Dacey Jr.

The authors propose a novel bibilometric index, the reverberation index (r-index), as a comparative assessment tool for use in determining differential reverberation between scientific fields for a given scientific entity. Conversely, this may allow comparison of 2 similar scientific entities within a single scientific field. This index is calculated using a relatively simple 3-step process.

Briefly, Thompson Reuters' Web of Science is used to produce a citation report for a unique search parameter (this may be an author, journal article, or topical key word). From this citation report, a list of citing journals is retrieved from which a weighted ratio of citation patterns across journals can be calculated. This r-index is then used to compare the reverberation of the original search parameter across different fields of study or wherever a comparison is required.

The advantage of this novel tool is its ability to transcend a specific component of the scientific process. This affords application to a diverse range of entities, including an author, a journal article, or a topical key word, for effective comparison of that entity's reverberation within a scientific arena. The authors introduce the context for and applications of the r-index, emphasizing neurosurgical topics and journals for illustration purposes. It should be kept in mind, however, that the r-index is readily applicable across all fields of study.

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Koichiro Ogura, Masakazu Takayasu, and Ralph G. Dacey Jr

✓ The effects of hypothermia and hyperthermia on the cerebral microcirculation were studied using isolated perfused intracerebral (parenchymal) arterioles obtained from rats. In a temperature-dependent manner, hypothermia (20.0° to 35.0°C) dilated the spontaneous tone developed by the arterioles and also diminished their contractile response to potassium and prostaglandin F. In contrast, hyperthermia (40.0° to 45.0°C) induced a biphasic response consisting of initial vasoconstriction and secondary vasodilation. Exposure of the vessels to 45.0°C for 30 minutes irreversibly abolished the spontaneous tone and responsiveness of the arterioles when the temperature of the preparation was returned to 37.5°C. In calcium-free solutions, however, the arteriolar diameter was not affected within a temperature range of 20.0° to 45°C. Furthermore, arterioles that had been in a calcium-free solution during exposure to 45°C temperature recovered their viability at 37.5°C. These results suggest that changes in ambient temperature alter calcium-induced contraction in arteriolar smooth muscle, and that the irreversible effects of hyperthermia on the arterioles are dependent upon extracellular calcium. These studies indicate that alterations in brain temperature may affect the pathogenesis of cerebral ischemia by mechanisms that are in part independent of parenchymal metabolism.

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Masakazu Takayasu, John E. Bassett, and Ralph G. Dacey Jr.

✓ There is no direct information on the effect of calcium antagonists on intracerebral penetrating arterioles, which are responsible for a significant part of total cerebrovascular resistance. In a study on rats, the effects of four calcium antagonists (diltiazem, verapamil, nifedipine, and nimodipine) on isolated intracerebral penetrating arterioles with mean resting diameters (± standard error of the mean) of 52.3 ± 3.0 µm were investigated. Vessel diameters were monitored in vitro by means of a video microscope dimensional analyzer under constant transmural pressure (60 mm Hg) after cannulation. Each calcium antagonist produced maximal dilation of about 50% (diltiazem 46.4% ± 5.6%, verapamil 53.1% ± 6.0%, nifedipine 46.9% ± 6.1%, and nimodipine 47.1% ± 5.4%) with varied sensitivity (median effective dose (ED50): diltiazem 1.52 × 10−6 M, verapamil 1.08 × 10−7 M, nifedipine 8.65 × 10−9 M, and nimodipine 1.62 × 10−9 M). Dilation effects persisted for a significantly longer time after washout with calcium antagonists such as diltiazem (15.5 ± 1.8 minutes), nifedipine (19.0 ± 3.9 minutes), and nimodipine (30.0 ± 1.6 minutes) than after washout with adenosine (8.5 ± 1.0 minutes). It appeared that the magnitude of vasodilation was greater and the duration of dilation after washout longer in intracerebral penetrating arterioles than that reported for pial arterioles, although sensitivity to each calcium antagonist was quite similar to that reported for larger cerebral arteries. These data provide a possible explanation for the apparent disparity between clinical efficacy and angiographically determined vessel diameter when patients with cerebral vasospasm are treated with calcium antagonists. These agents may have a greater effect on intracerebral penetrating arterioles than on angiographically visible larger arteries.

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Yasukazu Kajita, Hans H. Dietrich, and Ralph G. Dacey Jr.

✓ After subarachnoid hemorrhage (SAH), cerebral arteries display impaired vasomotor control, resulting in decreased regional cerebral blood flow. Recently, propagation of vasomotor responses has been recognized as an important regulatory mechanism in microcirculation. In this study, the authors tested the hypothesis that oxyhemoglobin (OxyHb) inhibits the vasodilatory effect of chemical mediators such as adenosine and adenine nucleotides at a local and/or propagated site.

Penetrating intracerebral arterioles were surgically isolated from the middle cerebral arteries of rat brains, cannulated, and observed videomicroscopically in an organ bath under an inverted microscope. The effects of 10−5 M OxyHb on vasoactive responses to adenosine, adenosine diphosphate (ADP), and adenosine triphosphate (ATP) were examined. The drugs were extraluminally applied either to the bath (10−10−10−3 M) or, using pressure microejection (pipette concentration 10−2 M), locally.

The ATP and ADP initially constricted and then significantly dilated the vessels after both extraluminal application and microapplication. Furthermore, local microstimulation by these drugs produced conducted vasodilation. Adenosine elicited significant vasodilation after both extraluminal and local stimulation. Again, conducted vasodilation was observed. The vasomotor responses that were induced by a maximum local stimulation corresponded in magnitude to those observed at bath concentrations of 10−5 to 10−4 M of the same drug.

Pretreatment with OxyHb constricted arterioles to an average of 87% of control and blunted extraluminally induced dilation at low concentrations (10−10−10−8) of ATP and ADP, but did not affect vasodilation induced by 10−4 M or greater concentrations of ATP, ADP, or adenosine. Although the local response to local microstimulation was unaltered, propagated vasodilation as a response to ATP, ADP, and adenosine was significantly attenuated by OxyHb.

These findings indicate that vasodilatory propagation plays an important role in the regulation of brain microcirculation and that its impairment by OxyHb could, in part, explain the cerebral hypoperfusion that is observed after SAH.

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Kent D. Yundt, Ralph G. Dacey Jr., and Michael N. Diringer

✓ The authors reviewed clinical and financial data for all patients treated for nontraumatic subarachnoid hemorrhage (SAH) and unruptured cerebral aneurysms at their institution between June 1993 and December 1994. This study sought to identify specific areas of high resource utilization that may be amenable to reduction of expenditures without compromising quality of care. Detailed hospital financial data were correlated with clinical grade and course. Areas of high resource use were identified based on patient charges and category-specific loaded hospital cost. Patients were divided into four groups: Group 1, surgically treated unruptured aneurysms (28 patients); Group 2, acute SAH (42 patients); Group 3, SAH with vasospasm (32 patients); and Group 4, SAH with negative angiogram (10 patients). Total cost per patient (mean ± standard deviation in thousands of U.S. dollars) was highest for Group 3 (38.4 ± 21.3; vs. Group 1, 12.7 ± 8.8; Group 2, 22.6 ± 20.9; and Group 4, 25.0 ± 33.5) and correlated with hospital length of stay, Hunt and Hess grade, and Fisher grade. Areas of highest hospital cost were not always reflected in patient charges. The three areas of highest cost accounted for 48.5% of the total cost and were: 1) intensive care unit (ICU) room (Group 1, 2.5 ± 3.5; Group 2, 7.0 ± 9.2; Group 3, 11.0 ± 7.8; and Group 4, 7.9 ± 14.1); 2) arteriography (Group 1, 1.7 ± 1.2; Group 2, 2.1 ± 1.5; Group 3, 4.1 ± 2.1; and Group 4, 2.2 ± 0.7); and 3) ICU medicosurgical supplies (Group 1, 1.7 ± 0.8; Group 2, 2.0 ± 1.5; Group 3, 3.7 ± 1.7; and Group 4, 2.0 ± 3.0). It is concluded that cost containment strategies should be based on cost rather than charge and novel approaches will be required to reduce the cost of treating patients with SAH. Such approaches might include preventing vasospasm, reducing ICU stay, selective use of arteriography, and reducing the cost of supplies.